Relationship between glutathione peroxidases family and survival prognosis in patients with colorectal cancer / 国际肿瘤学杂志

Objective:To investigate the relationship between glutathione peroxidases (GPXs) gene expression in colorectal cancer tissues and survival prognosis, and to construct and evaluate a nomogram prediction model of GPXs for survival prognosis of colorectal cancer patients.Methods:The GPXs gene expresion data and other clinical data of 620 patients with colorectal cancer (455 cases of colon cancer and 165 cases of rectal cancer) were downloaded from The Cancer Genome Atlas (TCGA) database, and the GPXs gene expression data of 820 normal people were downloaded as controls, preprocessed by R language, and the gene expression data were analyzed for differential expression. Spearman rank correlation was used to analyze the correlation between GPXs gene expression and tumor mutation burden (TMB) in colorectal cancer tissues. Cox risk regression model was used to analyze the influencing factors of survival and prognosis of colorectal cancer patients. Nomogram models were constructed to predict overall survival (OS) of colon cancer and rectal cancer patients, and its predictive performance was evaluated by calibration curve.Results:In the GPXs family, there were statistically significant differences in the mRNA expressions of GPX1, GPX2, GPX3, GPX4, GPX5, GPX7 and GPX8 between colon cancer patients and normal population, and the mRNA expressions of GPX1, GPX2, GPX4 and GPX8 in colon cancer patients were higher than those in normal population (all P<0.05) . There were statistically significant differences in the mRNA expressions of GPX1, GPX2, GPX3, GPX4, GPX7 and GPX8 between rectal cancer patients and normal population, and the mRNA expressions of GPX1, GPX2, GPX4, GPX7 and GPX8 in rectal cancer patients were higher than those in normal population (all P<0.05) . Spearman rank correlation analysis showed that GPX2 ( r s=-0.27, P<0.001) and GPX7 ( r s=-0.11, P=0.043) expressions were negatively correlated with TMB in colon cancer. There were no significant correlations between GPXs genes expressions and TMB in rectal cancer tissues (all P>0.05) . In colon cancer, univariate analysis showed that GPX3 ( HR=1.22, 95% CI: 1.05-1.43, P=0.012) , GPX4 ( HR=1.39, 95% CI: 1.01-1.92, P=0.045) , age ( HR=1.02, 95% CI: 1.01-1.04, P=0.010) and pTNM-stage ( HR=1.78, 95% CI: 1.43-2.21, P<0.001) were the influencing factors of OS. Multivariate analysis showed that GPX4 ( HR=1.96, 95% CI: 1.09-3.51, P=0.024) , age ( HR=1.02, 95% CI: 1.00-1.04, P=0.042) and pTNM-stage ( HR=1.61, 95% CI: 1.21-2.15, P=0.001) were the independent risk factors of OS. In rectal cancer, univariate analysis showed that age ( HR=1.08, 95% CI: 1.04-1.13, P<0.001) was the influencing factor of OS. Multivariate analysis showed that GPX7 ( HR=0.44, 95% CI: 0.22-0.88, P=0.020) , GPX8 ( HR=3.17, 95% CI: 1.63-6.17, P=0.001) and age ( HR=1.10, 95% CI: 1.04-1.16, P=0.001) were the independent influencing factors of OS. The consistency index (C-index) of the nomogram model for predicting OS in patients with colon cancer and rectal cancer were 0.71 (95% CI: 0.63-0.79) and 0.88 (95% CI: 0.82-0.94) respectively. The calibration curve showed that the prediction curve of the two models had a good fit with the real curve. Conclusion:GPX4 is an independent risk factor affecting the prognosis of colon cancer patients. Patients with high GPX4 expression have a poor prognosis. GPX7 and GPX8 are independent prognostic factors for rectal cancer patients, and the rectal cancer patients with low GPX7 expression and high GPX8 expression have poor prognosis. The nomogram constructed based on the above factors can better predict the prognosis of patients with colon cancer and rectal cancer.

Expression of Glutathione Peroxidases and Its Effect on Clinical Prognosis in Glioma Patients / 中国医学科学院学报

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.

Expression of glutathione peroxidases 4 in colon adenocarcinoma tissues and its relationship with clinicopathological features and prognosis of patients / 肿瘤研究与临床

Objective:To investigate the expression of glutathione peroxidases 4 (GPX4) in colon adenocarcinoma and its relationship with clinicopathological features and prognosis of patients.Methods:The data set of colon adenocarcinoma was obtained from The Cancer Genome Atlas (TCGA) database to analyze the expression of GPX4 in colon adenocarcinoma tissues and its predictive value for overall survival (OS). A total of 93 colon adenocarcinoma tissues and 87 adjacent mucosa tissues after operation from November 2009 to May 2010 provided by the National Human Genetic Resources Sharing Service Platform were selected. The expression of GPX4 protein was detected by using tissue chip immunohistochemistry. The relations between the expression of GPX4 protein and the clinicopathological features and OS of colon adenocarcinoma patients were analyzed. Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. The nomogram for predicting OS rate was established and drawn.Results:The analysis of data from TCGA database showed that in 380 cases of colon adenocarcinoma, the expression of GPX4 in colon adenocarcinoma tissues were higher than that in the normal colonic mucosa tissues [the value of fragments per kilobase of exon per million fragments mapped (FPKM): 85.654 (20.351-356.237) vs. 56.230 (48.783-63.931)], and the difference was statistically significant ( Z = -6.150, P<0.05). The OS in GPX4 high-expression group (FPKM ≥83.614) were poorer than that in GPX4 low-expression group (FPKM < 83.614) (median OS time: 84.40 months vs. 94.03 months, 5-year OS rate: 58.6% vs. 72.7%), and the difference was statistically significant ( P<0.05). Tissue chip immunohistochemical staining results show that the high-expression rate of GPX4 protein in colon adenocarcinoma tissues was higher than that in adjacent normal tissues [38.0% (35/92) vs. 7.3% (6/82)], and the difference was statistically significant ( χ2 = 22.727, P<0.01); the high-expression rate of GPX4 protein in left colon adenocarcinoma tissues was higher than that in right colon adenocarcinoma tissues [47.2% (25/53) vs. 25.6% (10/39), and the difference was statistically significant ( χ2 = 4.42, P = 0.036); the 5-year OS rate of patients in GPX4 high-expression group was lower than that in GPX4 low-expression group (25.7% vs. 57.9%), and the difference was statistically significant ( χ2 = 9.051, P<0.05). Multivariate Cox proportional hazards regression model analysis showed that lymph node metastasis (stage N 1-N 3) ( HR = 2.241, 95% CI 1.242-4.046, P = 0.007) and high expression of GPX4 ( HR = 2.783, 95% CI 1.598-4.848, P<0.01) were independent factors affecting the poor prognosis of colon adenocarcinoma patients. The above factors were used to establish a nomogram for predicting the prognosis of patients with colon adenocarcinoma, the C index was 0.739, indicating that the nomogram had good predictive performance. Conclusion:The expression of GPX4 is up-regulated in colon adenocarcinoma tissues, and its high expression is related to the malignant biological behavior of the tumor and poor prognosis.